From parasite genomes to one healthy world; are we having fun yet?

Authors: Zarlenga, Dante; Gasbarre, Louis

Submitted to: Veterinary Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/10/2009
Publication Date: 8/7/2009
Citation: Zarlenga, D.S., Gasbarre, L.C. 2009. From parasite genomes to one healthy world; are we having fun yet? Veterinary Parasitology. 163:235-249.

Interpretive Summary: Some applications of large scale sequencing have straightforward outcomes such as developing gene-based diagnostic tests; however, less direct benefits with equally important downstream applications involve studies on evolution, the host-pathogen interface, and marker development such as parasite drug resistance and host susceptibility to infection. Understanding population variation and how diversity can impact the “one-size-fits-all” mentality in designing 21st century diagnostics, drugs and immunotherapies is also receiving increased attention as more genome and transcriptome sequences become available. However, the lack of sequence congruence among different parasite genera is sufficiently large to defy the concept of a single model organism for use in comparative genomics which distances parasitology from large animal studies and technological applications. Thus the challenges facing those working on parasites as it relates to genetic variation are immense. Understanding this variability and its relationship to phenotype predictability will form a foundation for unilateral intervention strategies.The following presents new and reviewed data in applying parasite and host gene sequences to problem solving. Key research areas involve drug testing and design, evolution and population genetics, host-parasite relationships and epigenetics, and host resistance to parasites. Though applications of genomics to problem solving in parasitology have been slow to advance in areas other than DNA testing and diagnosis, they will in time become a requisite to understanding and creating a healthy world that has parasites as its nemesis. The information provided herein will be important in assisting those who wish to apply genomic information to problem solving in parasitology.

Technical Abstract: In 1990, the Human Genome Sequencing Project was established. This laid the ground work for an explosion of sequence data that has since followed. As a result of this effort, the first complete genome of an animal, Caenorhabditis elegans was published in 1998. The sequence of Drosophila melanogaster was made available in March, 2000 and in the following year, working drafts of the human genome were generated with the completed sequence (92%) being released in 2003. Recent advancements and next-generation technologies have made sequencing common place and have infiltrated every aspect of biological research, including parasitology. To date, sequencing of 32 apicomplexa and 24 nematode genomes are either in progress or near completion, and over 600K nematode EST and 200K apicomplexa EST submissions fill the databases. However, the winds have shifted and efforts are now refocusing on how best to store, mine and apply these data to problem solving. Herein we tend not to evaluate existing X-omics datasets or present technological advances that promise future benefits. Rather, the information to follow condenses up-to-date-applications of technologies conducted in our lab to problem solving as it relates to parasite research. Advancements in non-parasite systems are also presented with the proviso that applications to parasite research are in the making.